Histone acetylation and deacetylation appears to play a critical role in regulating transcriptional activation from chromatin templates. Studies from yeast have revealed that multiple histone acetyltransferases (HAT) and deacetylase complexes exist with the ability to modify specific combinations of lysine residues in the tails of histones.We have previously described four native nucleosomal HAT complexes with different target specificities, which generate unique patterns of acetylation and stimulate transcription invitro from chromatin templates. The discovery that the yeast transcriptional adaptor protein Gcn5 functions as the catalytic subunit in two of these complexes suggests that these complexes may be targetted to specific genes through interactions with transcription factors. Here we propose the analysis and identification of the components of a novel high molecular weight HAT complex, related to the Ada and SAGA HAT complexes which also apparently contains Gcn5 as the catalytic subunit. This complex is currently highly purified and in a state suitable for protein analysis by Mass spectrometry. These results should provide further insight into the role of HAT complexes in transcriptional activation and to the mechanism of their action.